The effectiveness of photodynamic therapy (PDT) depends on the simultaneous presence in the tumor tissue of photosensitizer, oxygen and light. Factors restricting either of these parameters will limit PDT. One such limiting factor may be the existence of hypoxic tumor cell regions, which may be present prior to PDT due to poor tumor blood supply, or which may be created early during tumor illumination due to the severe vascular damage induced by PDT. Another possibly limiting factor is the development of hemorrhage accompanying PDT-induced vascular damage which may restrict light penetration before a fully effective light dose has been delivered to the tumor cells. It is proposed to examine the extent and significance of these limitations to PDT treatment in vivo. The oxygen dependency of PDT treatment will be determined at cellular prophyrin concentrations obtained under in vivo porphyrin uptake conditions. The possible influence of pre-existing hypoxic tumor cell regions on in vivo PDT will be examined. The effect of vascular PDT damage on tumor oxygenation and the possible creation of acutely hypoxic tumor areas during PDT light delivery will be studied. It will be examined if tumor reoxygenation occurs following PDT. The changes in light penetration through skin and tumor tissue during PDT will be monitored, and light loss due to hemorrhage will be measured. The possibility that enhancement of tumor oxygenation by oxygen-carrying chemicals and high oxygen breathing may enhance photodynamic tumor destruction will be studied.